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A novel large animal model of recurrent migraine established by repeated administration of inflammatory soup into the dura mater of the rhesus monkey

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Neural Regeneration Research 2019年第1期14卷 100-106页

作者： Ning Chen Wei Su Shu-Hui Cui Jian Guo Jia-Chuan Duan Hong-Xia Li Li He Department of Neurology West China Hospital Sichuan University Department of Science & Technology West China Hospital Sichuan University National Chengdu Center for Safety Evaluation of Traditional Chinese Medicine West China Hospital Sichuan University

Several animal models of migraine have been established, and those based on trigeminovascular system activation are widely accepted. How- ever, most of these models have been established on lower animals, such as rodents, and involve only a single administration of a noxious stimulus. In this study, an inflammatory soup （10 μL）, consisting of prostaglandin E2 （0.2 mM）, serotonin （2 mM）, bradykinin （2 raM） and histamine （2 raM）, was injected into the dura mater of conscious rhesus monkeys through an indwelling catheter. The infusion started on day 8 and was repeated every 3 days, for a total of six administrations, to induce neurogenic inflammation. We performed behavioral assessments and measured the expression of the oncogene c-fos, neuronal nitric oxide synthase （nNOS） and calcitonin gene related peptide （CGRP） ill the trigeminal system and in multiple brain regions involved in pain processing by immunohistochemical staining. Compared with monkeys in the control group, three of the four animals in the inflammatory soup group displayed decreased motor behaviors, and two showed increased ipsilateral nose and mouth secretions during the stimulus period. Higher expression levels of c-fos, nNOS and CGRP were found in various brain areas of experimental animals compared with controls, including the trigeminal nucleus caudalis, thalamus, hypothalamus, midbrain, pons and other areas involved in pain perception. These results suggest that repeated inflammatory soup stimulation of the dura activates the trigeminovascular system and produces migraine-like pathological changes and abnormal behaviors in conscious rhesus monkeys.

关键词： nerve regeneration migraine rhesus monkey neurogenic inflammation cellular oncogene fos neuronal nitric oxide synthase calcitonin gene related peptide trigeminal system behavior immunohistochemistry neural regeneration

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